OP0034 IXEKIZUMAB IMPROVES SIGNS, SYMPTOMS, AND QUALITY OF LIFE IN PATIENTS WITH AXIAL SpA IRRESPECTIVE OF DISEASE DURATION: RESULTS FROM THE COAST-V, COAST-W AND COAST-X TRIALS
Authors: V. Navarro-Compán, J. D. Reveille, P. Rahman, J. Maldonado-Cocco, M. Magrey, R. Bolce, D. Sandoval, S. Y. Park, A. Kronbergs, M. Rudwaleit
Journal: Annals of the Rheumatic Diseases (2022)

Background Ixekizumab (IXE), a high-affinity monoclonal antibody selectively targeting interleukin-17A, 1 has demonstrated superior efficacy to placebo (PBO) in the treatment of patients (pts) with radiographic axial spondyloarthritis (r-axSpA) (COAST-V [ NCT02696785 ]; -W [ NCT02696798 ]), and non-radiographic axial spondyloarthritis (nr-axSpA) (COAST-X [ NCT02757352 ]). Objectives Assess treatment response to IXE categorised by disease duration since symptom onset (&lt;5 years (yrs), ≥5yrs) in pts with r-axSpA and nr-axSpA up to 52 Weeks (Wks). Methods Pts fulfilled ASAS classification criteria for r-axSpA or nr-axSpA and were randomised to receive 80mg subcutaneous IXE every 2Wks or 4Wks, or PBO (16Wks COAST-V/W; 52Wks COAST-X). Data were summarized by disease duration and treatment in eligible intent-to-treat (ITT) pts. Wk16 treatment comparisons were conducted using Cochran-Haenszel-Mantel test and ANCOVA. Missing data were handled using non-responder imputation and modified baseline observation carried forward, for categorical and continuous endpoints, respectively. Results Table 1 presents pt demographics and baseline characteristics. Data is from pooled IXE pts. In pts with r-axSpA and &lt;5yrs symptom duration, ASAS40 response was achieved by 51.5% at Wk16 and 60.6% at Wk52, compared to 36.9% at Wk16, significantly different to PBO (p&lt;0.001), and 40.5% at Wk52, in pts with ≥5yrs symptom duration. In pts with nr-axSpA and &lt;5yrs symptom duration, ASAS40 response was achieved by 42.5% at Wk16, significantly different to PBO (p=0.012), and 54.8% at Wk52, compared to 36.0% at Wk16 and 41.4% at Wk52 in pts with ≥5yrs symptom duration (Figure 1). In pts with r-axSpA and &lt;5yrs symptom duration, ASDAS LDA &lt;2.1 response was achieved by 39.4% at Wk16 and 48.5% at Wk52, compared to 27.5% at Wk16, significantly different to PBO (p&lt;0.001), and 35.6% at Wk52 in pts with ≥5yrs symptom duration. In pts with nr-axSpA and &lt;5yrs symptom duration, ASDAS LDA &lt;2.1 response was achieved by 32.9% at Wk16, significantly different to PBO (p=0.003), and 49.3% at Wk52, compared to 23.9% at Wk16 and 36.9% at Wk52 in pts with ≥5yrs symptom duration. At Wk16, in pts with r-axSpA pts and &lt;5yrs symptom duration, the Change from Baseline (CFB) in SF-36 Physical Component Summary (PCS) Score (LSM±SE) was 7.91 (±1.52), compared to 6.81 (±0.40) in pts with ≥5yrs symptom duration. In pts with nr-axSpA and &lt;5yrs symptom duration, this score was 8.95 (±0.95) compared to 7.07 (±0.73) in pts with ≥5yrs symptom duration; both were significantly different to PBO (r-axSpA: p&lt;0.001; nr-axSpA: p=0.037). Table 1. Patient demographics and Baseline Characteristics Pts with r-axSpA Pts with nr-axSpA &lt;5yrs (Ns=33 ) ≥5yrs (Ns=306 ) &lt;5yrs (Ns=73 ) ≥5yrs (Ns=111 ) Age (years ) 33.1 (8.15) 45.1 (12.12) 31.9 (10.07) 46.4 (11.86) Male, n (% ) 26 (78.8) 245 (80.1) 40 (54.8) 53 (47.7) Female, n (% ) 7 (21.2) 61 (19.9) 33 (45.2) 58 (52.3) Age at axSpA onset (years ) 30.4 (8.29) 27.0 (9.06) 29.9 (10.22) 29.5 (8.76) ASDAS score, mean (SD ) 3.87 (0.79) 4.03 (0.82) 3.79 (0.80) 3.85 (0.78) BASDAI score, mean (SD ) 7.16 (1.64) 7.25 (1.35) 7.00 (1.33) 7.30 (1.26) SF-36 PCS, mean (SD ) 34.02 (7.73) 32.86 (7.63) 32.84 (7.86) 32.57 (6.97) Abbreviations: IXE=ixekizumab, n=number of pts in specified category, Ns=number of pts in each subgroup, SD=standard deviation. Figure 1. ASAS40 Response Rates for patients with r-axSpA (COAST-V/W) and nr-axSpA (COAST-X) Symptom Duration &lt;5 and ≥5 years up to Week 52, ITT, NRI: Significantly greater response of IXE versus PBO at Week 16 denotated by * (p≤0.05), *** (p≤0.001). Abbreviations: PBO, placebo; IXE, Ixekizumab; NRI, nonresponder imputation; ITT, Intent-to-Treat (population), ASAS, Assessment of Spondyloarthritis International Society. Conclusion Efficacy response to the therapy with IXE was observed in both subgroups based on disease duration (&lt;5 and ≥5yrs) with more robust responses in the &lt;5 years subgroup. References [1]Paller AS, Br J Dermatol. 2020;183(2):231-241. Disclosure of Interests Victoria Navarro-Compán Speakers bureau: AbbVie, Janssen, Eli Lilly and Company, Novartis, Pfizer and UCB, Paid instructor for: AbbVie, Janssen, Eli Lilly and Company, Novartis, Pfizer and UCB, Consultant of: AbbVie, Eli Lilly and Company, Novartis, Pfizer and UCB, Grant/research support from: ASAS: Research grant 2018 and 2021. Novartis: Research grant 2021 (Payment to institution), John D Reveille Speakers bureau: Eli Lilly and Company and UCB Pharma, Consultant of: UCB Pharma, Grant/research support from: Eli Lilly and Company, Proton Rahman Speakers bureau: Abbott, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, and Company Janssen, Novartis, and Pfizer., Paid instructor for: Advisory Board: Abbott, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Novartis, and Pfizer., Grant/research support from: Janssen and Novartis, José Maldonado-Cocco Speakers bureau: Pfizer, Merck Sharp Dohme, Wyeth, Sanofi Aventis, Novartis, Bristol Myers Squibb, Roche, Shering-Plough, Abbvie, UCB, Gilead., Consultant of: Pfizer, Merck Sharp Dohme, Wyeth, Sanofi Aventis, Novartis, Bristol Myers Squibb, Roche, Shering-Plough, Abbvie, UCB, Gilead., Grant/research support from: Pfizer, Merck Sharp Dohme, Wyeth, Sanofi Aventis, Novartis, Bristol Myers Squibb, Roche, Shering-Plough, Abbvie, UCB, Gilead., Marina Magrey Speakers bureau: Novartis, Abbvie, Eli Lilly and Company., Consultant of: Novartis, Eli Lilly and Comapny, Pfizer, Janssen, UCB Pharma, Abbvie, BMS., Rebecca Bolce Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, David Sandoval Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, So Young Park Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Andris Kronbergs Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Martin Rudwaleit Speakers bureau: Abbvie, BMS, Boehringer Ingelheim, Chugai, Eli Lilly and Company, Novartis, Pfizer, UCB., Paid instructor for: Abbvie, Eli Lilly, Novartis, UCB., Consultant of: UCB, Grant/research support from: Galapagos, UCB, Novartis.